Zon-Mw TOP grant for research into the cause of Alzheimer’s

Prof. dr. Casper Hoogenraad (Utrecht University), Dr. Stefan Rüdiger (Utrecht University) and Dr. Ruud Toonen (VU Amsterdam) have jointly been awarded a Zon-Mw TOP grant of 675,000 euros. With this grant, they hope to be able to make a breakthrough in their research into the molecular cause of Alzheimer’s. The composition of their team is exceptional, and will provide an interdisciplinary perspective on this field of research.

TRANSPORT OF VESICLES

The millions of nerve cells in the human brain communicate through the fusing of vesicles at billions of synapses between the nerve cells. The mechanism by which vesicles are transported and delivered at the synapse is largely unknown. It is becoming increasingly clear that problems with vesicle transport are at the root of the occurrence of various diseases of the brain, such as Alzheimer’s disease. Hoogenraad, Rüdiger and Toonen research the way in which vesicles are propelled within the nerve fibres in the nerve cells of Alzheimer’s patients.

PREVENTING TAU PROTEIN AGGREGATION

It is known that clumps of the so-called Tau protein affect synapses and that this leads to detereoration of memory. That is why the research group wants to study the role of Tau protein in the process of vesicle transport. They are investigating whether it is possible to use chaperone proteins to prevent the aggregation of Tau protein, so that the transport system can recover. Chaperone proteins help proteins to fold and help to carry out quality control on existing proteins. Together with his colleagues, Rüdiger has already clarified the mechanism of binding between chaperone protein Hsp90 and Tau protein, which makes it possible to develop targeted substances that can influence the function of Hsp90. In this way, it may be possible to prevent the aggregation of Tau protein.

SCIENCE FOR LIFE

The research groups of Hoogenraad (Biodynamics and biocomplexity), Rüdiger (Cellular Protein Chemistry) and Toonen (Functional Genomics) are joining forces to use their research, Chaperoning axonal transport in neurodegenerative disease, to make steps towards treating Alzheimer’s disease. Eventually, they intend to unravel the mechanism responsible for the transport of vesicles to the synapses where signal transfer occurs, how this transport is affected in Alzheimer’s patients and how Tau protein aggregation can be manipulated to help treat disease related defects. This study is therefore a good example of Science for Life.